In this program project we have outlined a series of studies which may have potential use in the design of more optimal therapeutic approaches in selected human solid tumors. In the cell kinetics project, we wish to extend our previous work in the development of a comprehensive animal tumor kinetics model. An analysis of perturbation effects of drugs on cell cycle parameters in vitro and in vivo should result in a model which can predict drug effects in these and other models. The applicability of these data will be tested by human kinetics studies. A framework of unperturbed human kinetics data in lung, head and neck and breast cancer must be developed, and experiments detailing methodology and the kinds of human data necessary are outlined. Estrogen receptor kinetics studies proposed may provide a greater understanding of the nature of the receptor and its relationship to growth parameters of the tumors. These data will be collected in patients with metastatic breast cancer, and therapeutic changes on the receptor population will be monitored. The clinical designs in the three cancers attempt to improve therapeutic effects, or at least indicate the potential usefulness of certain modalities. They serve as a basis to test perturbation effects of modalities on cell populations and are easily modified as directions for more optimal designs become apparent.